Genetics Update

Mar

9

VoiceOfAmerica.com, March 6, 2009, by Zulima Palacio — Recently, the World Health Organization (WHO) announced that the emergence of parasites, along the Thai-Cambodia border, that are resistant to the medicine artemisinin could seriously undermine global malaria control.

The recent shift from drugs that were failing to the highly effective artemisinin-based combination therapies allowed great progress in fighting malaria, one of the world’s major killers.

More than one million people die of malaria each year, mostly in Africa.

The disease poses a risk to half of the world’s population, according to the World Health Organization

Now, along the Thai-Cambodian border, researchers have discovered a malaria parasite that is resistant to the most effective anti-malaria medicine.

Colonel Gray Heppner

Colonel Gray Heppner is a key researcher on malaria and Deputy Commander at the Walter Reed Research Institute in Maryland.

He says if drug resistance spreads, the number of yearly deaths could double.

“And it’s not just the death toll, it is the number of people who are chronically ill because we can’t cure them,” Heppner said. “So if you can imagine all the people that are chronically ill with malaria today. And some estimates are that there are a half a billion people that have a recognized episode of malaria every year. And if you think about doubling this, well it puts an incredible burden in a society.”

The recent news in a report by U.S. Army researcher Mark Fukuda, published in the New England Journal of Medicine, shows that some malaria parasites are resistant to artemisinin.

“The artemisinins are the most rapidly effective medicine that has ever been invented for malaria,” he said.

Artemisia plant

“Artemisia” is a plant. Its derivatives are known as artemisinins. The Chinese have used the plant for centuries against fever.

But a few decades ago, when malaria parasites became immune to chloroquine and other medications, artemisinin became the world’s great hope.

In the last decade, malaria control programs have also included insecticide-treated bed nets – to shield against mosquitos that carry the parasites. The nets and artemisinins have helped lower infection rates in many countries, mostly in Africa.

For the moment, there is no replacement for artemisinin-based drugs.

The Walter Reed Institute has been working to develop a vaccine against malaria as well as new medicines.

Colonel Peter Weina, who specializes in tropical diseases, and specifically malaria, led the U.S. Army’s effort to develop a drug against the most severe form of malaria. “Intravenous Artesunate” has not yet received final approval, but is now being use in certain cases.

“We have our formulation available on compassionate use here in the U.S. and recently in Canada. We have donated several hundred vials to clinical trials that are being done in Africa with some of our partner groups,” Dr. Weina said.

But this drug is also derived from artemisinin.

“There was an assumption and there was a hope and there was a prayer that resistance to artemisinin would never happen,” he said.

Child being treated for malaria

Research to find new medications against malaria continue.

“Out of every 5,000 compounds that show promise,” Dr. Weina said. “Only one of them statistically will make it to being a drug that is useful.”

The World Health Organization and the Bill and Melinda Gates Foundation have launched a multi-million dollar campaign to control the spread of the artemisinin resistant parasite.

But as Dr. Weina says, malaria is a disease of poverty. It thrives in areas lacking hygiene and resources. And it will be with us for years.

Definition of Artemisinin

MedicineNet.com — Artemisinin: An antimalarial agent extracted from the dry leaves of the Chinese herb Artemsisia annua (qinghaosu or sweet wormwood). This plant is grown each year starting from seed and only yields artemesinin under specific agricultural and climatological conditions. Wormwood is cultivated only in China, Vietnam and pilot projects in Tanzania and India. It takes eight months to mature.

Artemisinin acts rapidly and potently against the malarial parasite, including some drug-resistant strains. Without significant side effects, it quickly reduces fever and lowers the blood levels of the parasite. This help to keep small outbreaks of malaria from becoming epidemics and to quell ongoing epidemics. In a malaria epidemic in the early 1990’s in Vietnam, artemisinin reduced the death rate by 97%.

To decrease the risk of resistance, artemisinin is taken as part of a “cocktail.” The cocktail of artemisinin and lumefantrine (Benflumetol) is marketed as Coartem and Riamet. Artemisinin was first isolated in 1965 by Chinese military researchers. Pronounced ar-te-mis’-in-in with the accent on the mis.
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What is Artemisinin?

ScientificAmerican.com, December 2008, by Jordan Lite — Coartem, a malaria drug whose potency is derived from a Chinese herb, may soon be approved for sale in the United States.

DEADLY BITE The Food and Drug Administration may soon approve a drug derived from the herb artemisinin to treat malaria.
Public Health Image Library/James Gathany

The Food and Drug Administration (FDA) is poised to decide by Friday whether to green-light the use of the malaria drug Coartem as part of an expedited review reserved for life-saving treatments that the agency believes are more effective than existing therapies. An FDA advisory panel earlier this month overwhelmingly determined the drug to be safe and effective; the agency is not bound by recommendations but typically follows them.
Coartem, derived from the Chinese herb artemisinin, wipes out malaria in more than 96 percent of patients in regions where malaria has become resistant to older drugs, according to drug-maker Novartis. Traditional meds such as chloroquine work in only 50 percent of patients where the parasite is drug-resistant. There were an estimated 247 million malaria cases in 2006, and nearly 881,000 patients died, according to the World Health Organization.

Only around 1,500 people in the United States — mostly travelers returning from abroad or service members stationed in malaria hot spots — are diagnosed with the infection annually. But disease specialists said travelers might carry Coartem in case they contracted malaria — and bypass preventive meds such as Lariam, which can have psychological effects.

A Novartis spokesman said the company would release pricing information if Coartem receives FDA approval. We asked journalist Merrill Goozner, director of the Integrity in Science Project at the Center for Science in the Public Interest in Washington, D.C., who has covered the development of Coartem and written for ScientificAmerican.com on multi-drug resistant tuberculosis in Siberia, to tell us a bit more about it. Below is an edited transcript of our chat.

What is coartem?

It is a combination drug of two ingredients, neither of which has been approved in the U.S. One is artemether, a chemical derivative of artemisinin, an extract from the sweet wormwood bush that was used in Chinese medicine as a fever cure for 500 or 600 years. Artemether stays in the body for three days. The other is lumefantrine, a broad-spectrum antibiotic that stays in the body for about seven days. Coartem is the most effective treatment for Plasmodium falciparum malaria, the more lethal form.

Artemether is a very potent, but fast-clearing drug, which is why you take both it and lumefantrine. Malaria has a whole life cycle in the body; there can be slow-emerging parasites that can come out of the liver after three days, which is why it’s good to have the lumefantrine around a little longer. If anything should reemerge after three days, the lumefantrine will combat it.

Tell us a little bit about Coartem’s history.

Coartem was approved by the Swiss in the late 1990s and put on the World Health Organization (WHO) essential drug list in 2002, so it’s not a new drug by any stretch of the imagination.

It’s a combination pill. In a third-world setting where Coartem is primarily used, this is very convenient because it increases compliance.

It is the preferred treatment for falciparum malaria because many strains are resistant to choloroquine. As the strain developed resistance, there was a horrible need for new drugs, and this drug met it.

What would FDA approval do for Americans with malaria?

This is a drug of no consequence in the U.S. Artemether is available in intravenous form. If you were a hospital where a soldier were returning who had cerebral malaria, which is life-threatening, you could make a call to the Centers for Disease Control and tap its supply chain.

[The Tropical Disease Priority Review Voucher law, which took effect this fall, allows drug companies that develop treatments for neglected diseases like malaria an expedited review by the FDA. That means that in the future, Novartis can bring another, more lucrative drug candidate before the agency for quicker approval — or sell that right for hundreds of millions of dollars, Goozner says. “Yes, well, this is a gift from heaven,” Silvio Gabriel, who manages Novartis’ malaria initiatives, told today’s New York Times.